Fibers Released from Cigarette Filters: an Additional Health Risk to the Smoker?'

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[CANCER RE5EARCH 55, 253-258, January 15, 1995J Fibers Released from Cigarette Filters: An Additional Health Risk to the Smoker?'

John L. Pauly,2 Heather A. Allaart, Manuel I. Rodriguez, and Richard J. Streck

Departments of Molecular Immunology fJ. L P., H. A. A., R. J. S.J and Thoracic Surgery [M. I. R.J, Roswell Park Cancer Institute, New York State Department of Health, Buffalo, New York 14263

ABSTRACT adsorption (1, 4). When viewed with a white light microscope, the cellulose acetate fibers appear to have an internal channel-like struc Tests of 12 popular brands of cigarettes manufactured by 6 companies ture. This pattern is due to the image of one arm of the â€œYâ€•thatis from the United States have shown that fibers were released from the filters visible in the translucent fiber. Most other synthetic fibers are round, and that there exists probable cause to suggest that fibers are inhaled andlor ingested. Filter fibers, made of cellulose acetate, were Implanted in mice for ovoid, or serrated (13, 14), and we know of no other synthetic or 6months.Thefiberswithstooddegradationandretainedthetobacco-brownnatural fiber that has the same Y shape as that of the cigarette filter color and bright fluorescence ofthe tobacco tar that had been adsorbed from fiber. The Y shape, Ti02, and other features that are readily visible cigarette smoke, With a confocal laser scanning microscope, we have ob have enabled us to distinguish, microscopically, cigarette filter fibers served cigarette filter fibers In lung tissue from patients with lung cancer and from other synthetic as well as natural fibers. who were known to be habitual smokers. These findings raise the question as We report here that fibers are released from cigarette filters. This to whether fibers released from cigarettes further jeopardize the health of finding raises questions concerning the health risk of filter fibers that smokers and document the need to test components of cigarette filters for may be inhaled or ingested by the millions of people worldwide who toxicity and tumorigenicity. smoke filter cigarettes.

INTRODUCTION MATERIALS AND METHODS The filter cigarette was not a dominant factor in the marketplace Cigarettes Analyzed. Cigarettes used were purchased from local vendors. before the 1950s when it was thought to be â€œanoveltyitem directed The cigarettes included 20 different popular brands, and these brands were mainly at the women's marketâ€•(1) and commanded less than 1% of selected to represent the products of 6 different manufacturers in the United sales (1â€”4).At that time, the typical smoker preferred a 70-mm States. Smoked cigarettes were provided by adult volunteers or were obtained nonfilter cigarette (1). In response to emerging health concerns (5â€”7) with the use of a mechanical smoker. and the first report in 1964 by the Surgeon General on smoking and Cigarette Filter FIber IdentifIcation. Fibers from smoked and non health (8), acceptance of filter cigarettes increased rapidly (1, 4, 7, 9). smoked cigarettes were examined with a conventional fluorescence micro By 1983, approximately 95% of the cigarettes sold in the United scope that had been configured to provide mercury arc illumination, with filter States contained filters (1â€”4);thishigh percentage has been sustained configurationsoptimalfor FITC and TRITC,3and to producewhite light to the present (9). illumination (Reichert-Jung; Cambridge Instruments, Inc., Buffalo, NY). Human lung specimens were also examined with a Nikon Opitphot micro The purpose of the cigarette filter has been described in foreign and scope that had been interfaced with a MRC 600 argon laser microscope domestic patents (10â€”12).A patent awarded in 1956 in the United (Bio-Rad Microscience Division, Cambridge, MA). The details of this tech States to Knudson (10) stated that the cigarette filter was designed for: nology were reportedelsewhere(15). â€œtheremovalof any desired proportion of the tars and nicotine present Fibers were defined as a particle with a length:width ratio (i.e., aspect ratio) in tobacco smoke which account for its irritating properties and 3:1. Particles with an aspect ratio of less than 3:1 are defmed as structures. potential toxicity . . . and the remarkable nature of my invention that To delineate cigarette filter fibers from other fibers, we established the I can in fact achieve almost complete removal of the stated substances following criteria: (a) a central channel-like motif that reflects one arm of the and even within the limits imposed by practical factors such as the Y-shaped fiber; (b) Ti02 particle pattern; (c) fiber diameter; (d) arm diameter; necessity for maintaining a free draw. . . .â€œHowever,the author notes (e) translucence;(J) smooth fiber surface; and (g) bright fluorescence in the that â€œActually,ofcourse, complete removal of these substances is not TRITC and FITC filter configuration of filter fibers from smoked, but not from nonsmoked, cigarettes. desirable due to considerations of taste and flavor. Moreover, in the Evaluation of Filter Fiber Release. A study was conducted using ciga event all of the tars and nicotine are removed, no â€˜smoke'isproduced, rettes of 12 different brands to ascertain whether fibers were released from i.e., the smoker draws into his mouth only colorless and highly cigarette filters. Different tests performed in this study included the following unpalatable combustion gases.â€• analyses in which filter fibers were identified and enumerated with the use of The technology of making cigarette filters and the characteristics of a stereo-zoom microscope: for wrapper examination, filter fibers trapped the filter fibers have also been described in patents (10â€”12),and this between the cellophane wrapper and the unopened pack of cigarettes were subject has been summarized in a monograph (1). Filters of almost all counted; for residue observation, after the cigarettes were carefully removed cigarettes consist of fibers that are made of cellulose acetate, are from a pack, the residue (i.e., tobacco flakes and debris) at the bottom of the coated with the plasticizer triacetin to bind individual fibnls, and pack was poured onto a black paper and the number of filter fibers was contain the amorphous microparticulate (granule size, 1.0 pin) counted; in the tap test, a cigarette was placed in a plastic tube (diameter, 13 mm) and dropped 3.5 cm onto a black paper. Thereafter, the number of filter pigment Ti02 to provide a milk-white appearance (1, 4, 10â€”12).The fibers released was assessed; the drop test was similar to the tap test, but the standard filter contains approximately 16,000 fibers (fiber diameter, cigarette was released from a height of 15 cm; in the tongue test, the filter end â€”20â€”50p@m)(1, 4, 11). Filter fibers have a unique Y shape that has of a cigarette was touched to the tongue of a volunteer, and then a clean been engineered to maximize the surface area for tobacco tar microscope slide was pressed onto the same site. Thereafter, the number of fibers transferred from the tongue to the slide were delineated. To facilitate Received 7/1/94; accepted 11/11/94. screening different brands of filter cigarettes, a tissue test was established to The costs of publicationof this articlewere defrayedin partby the paymentof page replace the tongue test. In the tissue test, the filter end of a cigarette was charges.This articlemust thereforebe herebymarkedadvertisementin accordancewith 18 U.S.C. Section 1734 solely to indicatethis fact. 1 Supported in part by NIH Grant CA-16056. 3 The abbreviations used are: TRITC, tetramethylrhodamine 5-isothiocyanate; CLSM, 2 To whom requests for reprints should be addressed, at Department of Molecular confocal laser scanning microscope; PAH, polycyclic aromatic hydrocarbons; Md, Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. macrophage. 253

touched to the surface of a piece of bovine liver, and the number of filter fibers carefully from a pack that had been opened in the laboratory. Fibers that had been released was counted. were also released from cigarettes that had been smoked mechanically Fiber Degradation and Tar Retention Assessed in Mice. Filter fibers (Fig. 1B). from smoked, nonsmoked, or a mixture of both types of cigarettes were Filter Fibers of Smoked Cigarettes Fluoresce. Fibers of filters implanted i.p. or s.c. into mice. On different days thereafter, the fibers were from smoked and nonsmoked cigarettes could be distinguished easily. recovered and analyzed. Fibers in Human Lung Specimens. Patients were identified who were to Fibers of filters from nonsmoked cigarettes were translucent and clean undergo a lobectomy or pneumonectomy for removal of a lung cancer. Human (Fig. 1C). Fibers of filters from smoked cigarettes were also translu lung tissue from the surgical specimens was obtained with written informed cent; however, these fibers had a light brown residue caused by consent under approved investigative protocols. Freshly collected lung speci tobacco tar that had been adsorbed by the filter (Fig. 1C). Tobacco tar, mens that had not been fixed, sectioned, or stained were mounted in a viewing which is the particulate (i.e., nongas) phase of cigarette smoke (1, 8, chamber and examined with white light, polarizing, fluorescent, and confocal 9), adsorbed onto filter fibers is more easily recognized microscopi microscopes. Kodak Ektachrome film was used for photographic documenta cally when one examines a bundle of fibers. The tobacco brown of the tion and to record split-screen images of white and argon light views obtained adsorbed tar is readily apparent with the naked eye in a comparison of with a CLSM of cigarette filter fibers. A more complete description of these methods has been described elsewhere (15, 16). intact filters from a smoked and a nonsmoked cigarette. Tobacco tar tra@ on the surface of an individual filter fiber was RESULTS manifested more vividly by viewing the fibers with a fluorescence mi cmscope. Fibersoffilters from nonsmokedcigarettesdisplayedvery little Filter Fibers Identified within and upon Cigarette Packs. An or no fluorescence (Fig. 1D). In contrast, fibers of filters from cigarettes examination of 20 different brands of filter cigarettes revealed that the that had been smoked fluoresced briffiantly (Fig. U)). The intense fiuo filters consisted of a homogenous bundle of cellulose acetate fibers; rescence of the adsorbed tobacco tar was observed for fibers that were no other types of fibers were present. Moreover, the fibers from the viewed with either a FITC [fibers appeared green (Fig. 1D)] or TR1TC filters of various cigarettes were morphologically indistinguishable. [fibers appeared red (not shown)] filter configuration. Moreover, the From this group of 20 brands, 12 brands were selected for further intense fluorescence was also observed for fibers from low-tar cigarettes study. and cigarettes that had been smoked partially. In all instances (n = 24 packs; 12 different brands), we observed It is well known that the fluorochromes FITC and TRITC, used filter fibers located between the cellophane wrapper and the unopened commonly for labeling antibodies and other agents, are photobleached pack [9.83 Â± 8.0, (SD); range, 3â€”32Jand in the pack residue quickly. In contrast, the fluorescence of tobacco tar on the filter fibers (17.9 Â±8.4; range, 6â€”30)(Table 1). was not photobleached. The resistance to photobleaching was dem Tests Defining the Release of Filter Fibers. Filter fibers were onstrated by exposing a small segment of the filter fiber for a pro discharged from all cigarettes that had been tapped (3.44 Â±2.4; range, longed time (>15 min) to the argon laser of a CLSM or to the mercury 1â€”9;n= 60 cigarettes) or dropped (7.34 Â±4.0; range, 3â€”15)(Table1). arc illumination of a fluorescence microscope. Other tests were conducted to determine whether filter fibers were The fluorescence of fibers from smoked cigarettes was caused by released if touched to the tongue as may occur during smoking. A adsorbed tobacco tar. This was demonstrated by eluting the adsorbed procedure was established in which the filter end of a cigarette was tobacco tar from filter fibers with methanol or other solvents. After the touched to the tip of the tongue; immediately thereafter, a microscope tobacco tar was washed off, the fiber retained its characteristic mor slide was touched to this same site. In all instances, the microscope phology but did not fluoresce. slide contained cigarette filter fibers. In subsequent experiments, we Filter Fibers Resist Degradation and Retain Tobacco Tar. observed that a larger number of fibers were recovered from the Having observed that fibers were released from cigarette filters, we tongue using clear, polypropylene package-sealing tape than could be conducted tests to determine whether the fibers resisted degradation obtained with a microscope slide. and retained the adsorbed tobacco tar. To extend our findings of fibers released from cigarette filters in the In all instances, ifiter fibers that had been implanted i.p. or s.c. tongue test and to facilitate counting the fibers, subsequent experi became encapsulated (Fig. 2A). Histological examinations of the ments were conducted in which the ifiter end of the cigarette was capsule (Fig. 2B) showed that the implanted fibers had become touched to the surface of bovine liver. In all instances, fibers were surrounded and enmeshed in tissue containing collagen, fibroblasts, detached from cigarette filters (14.0 Â±3.4; range, 9â€”19;n = 60 and M4 (Fig. 2B; harvest day 183). The high-power view of Fig. 2B cigarettes) (Table 1). In tests of both smoked and nonsmoked ciga also illustrates the Y shape of the filter fibers as well as the Ti02 rettes, we also noted that additional fibers were released when the pigment. same filter had been touched to either the tongue or tissue a second Fibers implanted i.p. or s.c. in mice showed no evidence of degra and third time. dation (Fig. 2, Bâ€”D).In addition, the fibers retained their tobacco Fibers were observed protruding from cigarette filters. Fig. IA brown color (Fig. 2C). The absence of fiber degradation and retention illustrates displaced filter fibers of a cigarette that had been removed of tobacco tar were recorded for groups of mice (n = 6) in which the

testsCigaretteCigaretteTable 1Cigarette filterfibers observed in cigarettepack wrapping and pack residue and released in tap, drop, and tissue releasedManufacturerâ€•Brmd@'Wrappedâ€•Residueâ€•TspCj@pCTissuec1â€”VIAâ€”L9.83 filter fibers

Â±8.0â€• Â±8.4 Â±2.4 Â±4.0 Â±3.4 [email protected] 6â€”303.44 1â€”97.34 3â€”1514.0 9â€”19

a N = 12 brands total; 2 brands from each of 6 different manufacturers in the United States. bN = 24 packs (12 brands).

C N = 60 cigarettes (12 brands). Mrm Â±SD. e Range. 254

FIBERS RELEASED FROM CIGAREITE FILTERS

Fig. 1. Morphology and fluorescence of ciga rette filter fibers. A, fibers protruding from a A@B cigarette filter (filter diameter, 8 mm); B, a filter fiber, coated with tobacco tar, that had been released from a cigarette that had been smoked mechanically. The displaced fiber was captured with a fme-mesh screen and was viewed with a fluorescence microscope equipped with a FITC filter configuration. X 100; C, a view with a white light microscope of four cigarette filter fibers. Two of the fibers were from a nonsmoked cigarette and two of the fibers were from a smoked cigarette. Arrows identify the appearance of the channel-like motif in the center of the fibers; this structure reflects the unique Y-shape morphology of the translucent fiber. Also shown D are the pepper-like grains of the Ti02 pigment that is added to the cellulose acetate polymer to give the filter fiber a white appearance. X 200; @ D, the same microscope field as that of C but ! observed with a fluorescence microscope with a FITC filter configuration. The two fibers from the smoked cigarette display a high level of flu orescence (green) that emanates from tobacco tar that has been adsorbed onto the filter fibers from cigarette smoke. In contrast, the fibers from the nonsmoked cigarette do not fluoresce and, thus, are not visible x 200.

fibers were harvested after 57 and 183 days. The bright fluorescence identify cigarette filter fibers. A criterion was established (see â€œMa of adsorbed tobacco tar was observed with either a FITC (Fig. 2D) or terials and Methodsâ€•)whereby cigarette filter fibers were distin TRITC (not shown) configuration. guished from other fiber types. Other experimental groups consisted of mice that had received a Shown in Fig. 3 are split-screen images obtained with a CLSM mixture of fibers from smoked and nonsmoked cigarettes. Fibers that of cigarette filter fibers present in fresh human lung tissue. Fig. 3A had been retrieved 6 months later from the mice could be distin is a white light and fluorescent light, low-power view of a cigarette guished easily by fluorescence microscopy. filter fiber in a fresh human lung specimen. Fig. 3B is a similar Cigarette Filter Fibers Observed in Human Lung Tissue. Spec view of another fiber, but this fiber is shown at a higher magnifi imens of lung tissue that had been freshly collected and that had not cation so as to illustrate features characteristic of a cigarette filter been fixed, sectioned, or stained were examined with a CLSM to fiber.

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Fig. 2. Filter fibers of smoked cigarettes that had been implanted into mice. A, a view of ifiter fibers that had been placed into the peritoneum of a mouse and harvested after 57 days. The filter fibers had become encapsulated. Arrow, capsule located on a bed of fat (mm scale); B, section (10 @mthick)of a wax block histological preparation of encapsulated cigarette filter fibers harvested after 183 days. In all instances, fibers that had been implanted into the peritoneum or s.c. (n 6 mice) became encapsulated, showed no evidence of degradation, and retained the adsorbed tobacco tar. The arrow identifies one of eight ifiter fibers, that have been transversely cross-sectioned. This view illustrates the unique Y-shapc morphology of cigarette filter fibers. The Ti02 pigment of the filter fibers is also illustrated; the pigment appears as amorphous black specks within the fiber. There was no evidence of fiber degradation. The capsule was similar to that shown in A. The filter fibers had been entwined in a heterogeneous tissue that contained fibroblasts. H & E, X 200; C, a view with a white light microscope of cigarette filter fibers that had been isolated with forceps from the tissue capsule. There was no evidence of fiber degradation. Also, the fibers were tobacco-brown, and there was no perceptible reduction in the amount of adsorbed tobacco tar. X 200; D, the same microscope field as that of C but observed with a fluorescence microscope with a FITC filter configuration. The high level of fluorescence further documented the retention in vivo of the tobacco tar that had been adsorbed onto the fibers during smoking. X 200. 255

We have demonstrated that fibers are released from the ifiters of @@ /@ @b5.,u â€¢.--- popular American cigarettes. In these experiments, we used cigarettes from packs that had been opened carefully in our laboratory. Larger numbers of fibers would be expected to be released by cigarettes that sib had been distressed; e.g., when a cigarette pack is dropped, crushed, or damaged in some other manner as may occur during daily activities. We have observed filter fibers between the cellophane wrapper and the unopened pack. This would suggest that cellulose acetate fibers are present as airborne contaminants in the high-speed filter cigarette making (>10,000/mm) and cigarette packaging operation. Filter fibers were also discovered in the residue of all packs examined. Presumably, these fibers were released from the ciga rettes during packaging or shipping. Our tests also revealed that filter fibers were dislodged when the cigarettes were tapped or dropped. We have shown that cigarette filter fibers became detached when B@ the ifiter was touched to the human tongue or bovine liver. In related experiments, cigarettes with recessed filters were also evaluated in the tongue and tissue tests. The tipping paper of the recessed filter prevented the fiber bundle from touching the tongue and tissue, and no ,â€˜ 1@'. fibers were released. Thus, the recessed filter provided a safeguard ,@, against contact-associated fiber release. @â€˜\I Having established that cigarette filter fibers are likely to be inhaled @- @* . @@ â€˜ I.. 4 or ingested, experiments with mice were undertaken to define whether the fibers were degraded in vivo. No degradation was detectable. The absence of cellulose acetate fiber deterioration in vivo was not unex pected, and we know of no mechanism(s) whereby these acetylated polysaccharide fibers would be biodegraded under physiological conditions. @Ã§:.t,_ We also noted that the filter fibers that had been implanted in mice for 6 months exhibited their characteristic tobacco-brown color and bright fluorescence, thus illustrating that tobacco tar had been retained Fig. 3. Cigarette filter fibers present in human lung tissue are illustrated in split-screen images obtained with an argon laser scanning microscope. A, a low-power view obtained on the filter fiber. with an argon laser of a cigarette filter fiber in a fresh, nonfixed, and nonstained lung The presence of fluorescent PAH in tobacco tar has been well tissue (left). One arm of the Y-shaped, translucent cigarette filter fiber appears as a channel-like structure (two arrows). A single, confocal, optical section (thickness, 5 gtm) documented (9, 20â€”24).About a dozen PAH have been identified of the lung tissue (right) illustrates the high level of fluorescence (FITC configuration) of in cigarette smoke (20â€”24),and several of these PAH [e.g., 3,4- the fiber at left. Fiber diameter, 32 @im(see scale bar); B. a high-power picture acquired benzo(a)pyrene] have been shown to be human carcinogens (9, with an argon laser of a lung tissue specimen exhibiting more fully the unique features of an inhaled cigarette filter fiber (left). The channel-like structure of the Y-shaped cigarette 20â€”24). fibers is apparent (bar, 6 sm). Arrow, prominent Ti02 granules. A single optical section Other investigators have documented the adsorption of PAH and (2 @sm)ofthe tissue obtained with the microscope in the confocal mode (right). This view tobacco-specific N-nitrosamines as well as different heavy metals to shows the bright fluorescence of the cigarette filter fiber (FITC configuration). Fiber diameter, 20 gim (see scale bar). cellulose acetate cigarette filter fibers (9, 22). We have observed cigarette filter fibers in human lung specimens. We acknowledge, nevertheless, that microscopic screening of lung DISCUSSION specimens for inhaled fibers is labor intensive and unsuitable for quantitative analyses. To this end, additional techniques must be In a previous study, we examined freshly excised human lung tissue established for the identification and enumeration of different syn with the intent of defining the most suitable method of isolating M4 thetic and natural fibers. A method that we are exploring is one in (17).Thegoalofthisstudywastoidentifytheexpressionofsurface which a 0.5-g human lung specimen is digested and the fibers present membrane cytokine receptors and to formulate a mixture of human in the residue are collected onto a micropore filter. Thereafter, the recombinant cytokines that could be delivered as an aerosol to achieve classification and unequivocal identification of various fibers may be the in situ, site-specific activation of human lung M4 (18). In these achieved with combined microscopic and spectrophotometric analy experiments, a fresh, nonfixed, and nonstained lung specimen was ses such as those of established protocols that are used by forensic placed in a viewing chamber and examined with a fluorescence pathologists (13, 14).@Delineation of the health risks will require microscope. A fluorescence microscope was chosen to screen differ correlating fiber burden with the pathological findings, clinical obser ent lung specimens because it has been known for many years that vations, and medical, occupational, and behavioral history of the lung M4 of habitual smokers display a high level of fluorescence; we patient. (17) and others (19) have attributed the fluorescence primarily to The following multicomponent hypothesis has been defined: (a) ingested tobacco tar. Our inspection of fresh human lung tissue filter fibers are released from cigarettes and are ingested and/or revealed the presence of fluorescent fibers. This serendipitous obser vation prompted us to inquire as to whether these fibers were inhaled 4 i. L Pauly, H. M. Jezewski, M. I. Rodriguez, E. L Hurley, and R. J. Streck. Inhaled cigarette filter fibers and inspired us to undertake the study reported natural and synthetic fibers identified in fresh, non-fixed, and non-stained human lung herein. specimens, submitted for publication. 256

Downloaded from cancerres.aacrjournals.org on September 28, 2021. © 1995 American Association for Cancer Research. FIBERS RELEASED FROM CIGARE1'FE FILTERS inhaled; (b) fibers that have been inhaled resist degradation and knowledge that tobacco tar contains adsorbed onto filter fibers may be sequestered in the lung of smokers for a prolonged time, contains carcinogens [e.g., PAH and 4-(methylnitrosamino)-1-(3- possibly for life; (c) fibers may accumulate in large numbers, pyridyl)-1-butanone] and toxins; (d) cigarette filter fibers im particularly in the lungs of habitual smokers whose clearance planted in mice for a prolonged time retained their morphology and mechanism has been impaired by smoking; (d) inhaled cigarette adsorbed tobacco tar and thus the cellulose acetate fibers resist fibers may induce acute and/or chronic inflammation; (e) different biodegradation; and (e) cigarette filter fibers have been identified chemicals in the tar that had been adsorbed onto the fibers (e.g., in human lung specimens. These findings establish the need for PAH, tobacco-specific N-nitrosamines, heavy metals, phenols, studies analyzing the toxicity and tumorigenicity of cigarette filter etc.) are released, possibly at variable rates, into the adjacent components. microenvironment, and (f) the slow release of carcinogens and tumor promoters may induce and/or accelerate malignant transfor mation; moreover, the nondegradable fiber and the discharge of ACKNOWLEDGMENTS various tar-associated toxins and heavy metals may provoke chronic inflammation. We acknowledge the participation of Edward Hurley, Cell Analysis Facility; Carlos Perez-Mesa, Department of Clinical Pathology; Harry Filter cigarettes have evolved through several steps (1). The first Slocum, Tissue Procurement Program; and Jan Vaage, Department of was probably the use of tipping papers that had been selected to Experimental Pathology, all of the Roswell Park Cancer Institute. We also prevent the cigarette from sticking to the lip of the smoker. The thank the following for their critical review of the manuscript: Dietrich second step was the addition of a stiff paper tube at the end of the Hoffmann, American Health Foundation, Vahalla, NY; Bruce Johnson, cigarette; this tube acted as a built-on holder and prevented sticking. Lung Biology Section, National Cancer Institute-Navy Medical Oncology A third step was the insertion of a small wad of cotton fiber in the Branch, Bethesda, MD; K. Michael Cummings, Cancer Control and Epi paper tube placed up against the tobacco column. This tuft of fiber demiology, Roswell Park Cancer Institute; and Victor Roggli, Department performed the further function of retaining any loose particles of of Pathology, Duke University, Durham, NC. tobacco that might enter the mouth of the smoker and may have had some ifiter effect. Paper and cotton filters have also been used; these preceded the introduction of the cellulose acetate filters. The smoker REFERENCES has preferred the taste of acetate-filtered smoke and the neat 1. Browne, C. L The Design of Cigarettes, Ed. 3, pp. 1â€”119.Charlotte, NC: Filter appearance of the typical acetate filter tip (1). Products Division, Hoechst Cellanese Corp., 1990. 2. Anonymous. Production of cigarettes. Import and export of cigarettes, 1992. Tobacco Many other changes have occurred in both the composition and J. Int., 6: 60â€”62,1992. design of the cigarette (1, 25). A partial listing includes variation in 3. Anonymous. Production of cigarettes. Import and export of cigarettes, 1993. Tobacco J. tnt., 1: 40â€”42,1993. tobacco type, blend, and processing; reduction in tar and nicotine 4. Browne, C. L The making and use of cellulose acetate tow. World Tobacco, 3: delivery; and the incorporation of reconstituted tobacco, expanded 45â€”52,1989. tobacco, as well as different chemical â€œadditives.â€•Likewise,the 5. Doll, R., and Hill, A. B. Smoking and carcinoma of the lung. A preliminary report. Br. Med. J., 2: 739â€”748,1950. design of the cigarette has changed (e.g., paper porosity, side venti 6. Wynder, E. L, and Graham, E. G. Tobacco smoking as a possible etiological factor lation, column length and diameter, and charcoal filter). These in bronchogenic carcinoma. JAMA, 143: 329â€”336,1950. 7. Slade, J. The tobacco epidemic: lessons from history. J. Psychoact. Drugs, 21: changes have been shown to alter smoking behavior (9). Taking into 281â€”291,1989. account these variables as well as the complex nature of cigarette 8. United States Public Health Service. Smoking and Health. 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John L. Pauly, Heather A. Allaart, Manuel I. Rodriguez, et al.

Cancer Res 1995;55:253-258.

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